Towards a Swiss health study with human biomonitoring: Learnings from the pilot phase about participation and design.

BACKGROUND: A large-scale national cohort aiming at investigating the health status and determinants in the general population is essential for high-quality public health research and regulatory decision-making. We present the protocol and first results of the pilot phase to a Swiss national cohort aiming at establishing the study procedures, evaluating feasibility, and assessing participation and willingness to participate. METHODS: The pilot phase 2020/21 included 3 components recruited via different channels: a population-based cross-sectional study targeting the adult population (20-69 years) of the Vaud and Bern cantons via personal invitation, a sub-study on selenium in a convenience sample of vegans and vegetarians via non-personal invitation in vegan/vegetarian networks, and a self-selected sample via news promotion (restricted protocol). Along with a participatory approach and participation, we tested the study procedures including online questionnaires, onsite health examination, food intake, physical activity assessments and biosample collection following high-quality standards. RESULTS: The population-based study and the selenium sub-study had 638 (participation rate: 14%) and 109 participants, respectively, both with an over-representation of women. Of altogether 1349 recruited participants over 90% expressed interest in participating to a national health study, over 75% to contribute to medicine progress and help improving others' health, whereas about one third expressed concerns over data protection and data misuse. CONCLUSIONS: Publicly accessible high-quality public health data and human biomonitoring samples were collected. There is high interest of the general population in taking part in a national cohort on health. Challenges reside in achieving a higher participation rate and external validity. For project management clear governance is key.

The Bland-Altman method should not be used when one of the two measurement methods has negligible measurement errors.

BACKGROUND: The Bland-Altman limits of agreement (LoA) method is almost universally used to compare two measurement methods when the outcome is continuous, despite warnings regarding the often-violated strong underlying statistical assumptions. In settings where only a single measurement per individual has been performed and one of the two measurement methods is exempt (or almost) from any measurement error, the LoA method provides biased results, whereas this is not the case for linear regression. METHODS: Thus, our goal is to explain why this happens and illustrate the advantage of linear regression in this particular setting. For our illustration, we used two data sets: a sample of simulated data, where the truth is known, and data from a validation study on the accuracy of a smartphone image-based dietary intake assessment tool. RESULTS: Our results show that when one of the two measurement methods is exempt (or almost) from any measurement errors, the LoA method should not be used as it provides biased results. In contrast, linear regression of the differences on the precise method was unbiased. CONCLUSIONS: The LoA method should be abandoned in favor of linear regression when one of the two measurement methods is exempt (or almost) from measurement errors.

The Corona Immunitas Digital Follow-Up eCohort to Monitor Impacts of the SARS-CoV-2 Pandemic in Switzerland: Study Protocol and First Results.

Objectives: To describe the rationale, organization, and procedures of the Corona Immunitas Digital Follow-Up (CI-DFU) eCohort and to characterize participants at baseline. Methods: Participants of Corona Immunitas, a population-based nationwide SARS-CoV-2 seroprevalence study in Switzerland, were invited to join the CI-DFU eCohort in 11 study centres. Weekly online questonnaires cover health status changes, prevention measures adherence, and social impacts. Monthly questionnaires cover additional prevention adherence, contact tracing apps use, vaccination and vaccine hesitancy, and socio-economic changes. Results: We report data from the 5 centres that enrolled in the CI-DFU between June and October 2020 (covering Basel City/Land, Fribourg, Neuchâtel, Ticino, Zurich). As of February 2021, 4636 participants were enrolled and 85,693 weekly and 27,817 monthly questionnaires were collected. Design-based oversampling led to overrepresentation of individuals aged 65+ years. People with higher education and income were more likely to enroll and be retained. Conclusion: Broad enrolment and robust retention of participants enables scientifically sound monitoring of pandemic impacts, prevention, and vaccination progress. The CI-DFU eCohort demonstrates proof-of-principle for large-scale, federated eCohort study designs based on jointly agreed principles and transparent governance.

A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma.

The detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies in the serum of an individual indicates previous infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral spike protein are more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, inflexible, and potentially biohazardous. Here, we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor. This high-throughput method matches the performance of the gold standard live virus infection assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific immunoglobulin G titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 spike protein variants of concern. We used our assay to profile serum samples from 59 patients hospitalized with coronavirus disease 2019 (COVID-19). We found that although most sera had high activity against the 2019-nCoV parental spike protein and, to a lesser extent, the α (B.1.1.7) variant, only 58% of serum samples could efficiently neutralize a spike protein derivative containing mutations present in the ß (B.1.351) variant. Thus, we have developed an assay that can evaluate effective neutralizing antibody responses to SARS-CoV-2 spike protein variants of concern after natural infection and that can be applied to characterize vaccine-induced antibody responses or to assess the potency of monoclonal antibodies.